Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study.

BACKGROUND: Ultrafast computed tomography (CT), by acquiring images of the proximal coronary arteries, detects coronary calcifications and has been demonstrated to be highly sensitive for the detection of coronary artery disease in many small studies. The aim of this study was to determine the relationship between ultrafast CT scanning and coronary angiography in a large number of symptomatic patients. METHODS AND RESULTS: The study population consisted of 710 patients from six participating centers. A multivariate logistic regression model was used to evaluate the individual contributions of age, number of calcified vessels, and the calcium score for the probability of angiographically significant disease. Of the 710 patients enrolled, 427 patients had significant angiographic disease, and coronary calcification was detected in 404, yielding a sensitivity of 95%. Of the 23 patients without calcifications, 19 (83%) had single-vessel disease at angiography. Of the 283 patients without angiographically significant disease, 124 had negative ultrafast CT coronary studies, for a specificity of 44%. An increasing number of vessels with calcification present on ultrafast CT was found to increase specificity for the presence of obstructive coronary artery disease in at least one vessel (P < .0001). As the log of the calcium score increases, the probability of multivessel obstructive disease increases (P < .0001). CONCLUSIONS: Ultrafast CT scanning is an noninvasive, non-exercise-dependent test with an excellent sensitivity for the detection of coronary artery disease. The presence of calcifications in multiple vessels and in younger populations correlates with higher specificities for obstructive disease, making ultrafast CT coronary scanning a very useful diagnostic test.

Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography.

OBJECTIVES: This investigation sought to determine the relative prognostic value of coronary calcific deposits and coronary angiographic findings for predicting coronary heart disease-related events in patients referred for angiography. BACKGROUND: The relation among coronary calcification, coronary stenoses and coronary heart disease-related events is of interest on a clinical as well as a pathophysiologic basis. METHODS: Four hundred ninety-one symptomatic patients underwent coronary angiography and electron beam computed tomography at five different centers between April 1989 and December 1993. The electron beam computed tomograms were interpreted by a cardiologist with no knowledge of the coronary angiographic and clinical data. Receiver operating characteristic (ROC) curves were constructed to determine the relation between electron beam computed tomographic and coronary angiographic findings. A follow-up telephone survey was completed in 86% of patients. The records for all patients who died or were admitted to the hospital for chest pain or suspected myocardial infarction were reviewed by three other cardiologists with no knowledge of the coronary angiographic and electron beam computed tomographic study results. RESULTS: The mean (+/- SE) area under the ROC curve was 0.75 +/- 0.02 for the coronary calcium score, indicating moderate discriminatory power for this score for predicting angiographic findings. Thirteen coronary heart disease-related deaths and eight nonfatal acute infarctions occurred over 30 +/- 13 months. Scores were sorted in ascending order and divided into quartiles of equal size. One patient in the first quartile had a fatal myocardial infarction (coronary calcium score range 0 to 2.1); 2 in the second quartile (range 2.1 to 75.3), 8 in the third quartile (range 75.3 to 397.1) and 10 in the fourth quartile (> 397.1) had a coronary heart disease-related event. Application of bivariate logistic regression showed that log score but not number of angiographically diseased vessels significantly predicted the probability of a coronary heart disease-related event occurring during follow-up. CONCLUSIONS: Electron beam computed tomographic calcium scores correlate moderately well with angiographic findings. These scores predict coronary heart disease-related events in patients undergoing angiography as well as do the number of angiographically affected arteries.

Ultrafast computed tomography for detection of coronary artery calcification.

This review summarizes coronary artery calcification as a marker of coronary atherosclerosis as historically noted and detected with radiographic imaging modalities. This review concentrates on the use of ultrafast computed tomography (CT) for coronary artery calcification imaging. Ultrafast CT is uniquely qualified for imaging of the coronary arteries and calcific deposits in particular because of the x-ray attenuation characteristics of calcium. Current validation studies are summarized. In particular, the sensitivity of ultrafast CT coronary calcification in angiographically proven obstructive disease has been shown by many investigators to be above 90%, but with specificity on the order of 40% to 50%. These numbers may be different for younger men and women, where the detection of smaller calcific deposits is more difficult. The positive predictive value has been calculated as between 72% by angiographic validation and 40% in a population with a lower pretest bias.

Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension.

The effort limitation in primary pulmonary hypertension (PPH) is thought to result from an inability to increase cardiac output with exercise. The precise mechanism, however, is unknown. We studied right ventricular (RV) and left ventricular (LV) function and interactions in 16 patients with PPH with electron beam computed tomography (EBCT) at rest and during supine bicycle exercise. RV and LV volumes and masses were measured at systole and diastole, and ejection fraction and cardiac index computed. Resting RV end-diastolic volume (215 +/- 72 ml) and mass (110 +/- 45 g) were increased, whereas stroke volume (65 +/- 26 ml) and ejection fraction (31 +/- 8%) were decreased. LV end-diastolic volume (80 +/- 31 ml) was decreased, whereas ejection fraction remained normal (66 +/- 9%). Cardiac index was at the lower limit of normal (2.26 +/- 0.72 L/min/m2). During exercise, RV end-diastolic volume was unchanged (196 +/- 63 ml, p = NS) but stroke volume (52 +/- 29 ml, p < 0.05) and ejection fraction (26 +/- 10%, p = 0.08) decreased. LV end-diastolic (52 +/- 22 ml, p < 0.001), end-systolic (17 +/- 8 ml, p < 0.001), and stroke volumes (35 +/- 20 ml, p < 0.001) decreased, whereas ejection fraction (65 +/- 15%, p = NS) and cardiac index remained unchanged (2.17 +/- 0.93 L/min/m2, p = NS). the ratio of RV/LV stroke volume at rest (1.21 +/- 1.06) increased with exercise (1.74 +/- 1.13, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography.

OBJECTIVES: This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND: Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS: Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS: Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS: Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Ultrafast computed tomography for the physiological evaluation of myocardial perfusion.

Quantitation of myocardial blood flow has been sought by the clinician using a variety of imaging modalities and blood indicator dilution techniques. Ultrafast computed tomography has real potential for clinically useful estimations of regional myocardial blood flow. At the present time, there are limitations with this technique and early washout of indicator (iodine) appears to be the most likely explanation for the inaccuracies observed. Several methods have been tried to correct for early washout without success. Preliminary data based on a new algorithm look promising. Currently available techniques for detecting and quantifying myocardial ischemia have significant limitations. A noninvasive method able to determine wide ranges of flow with accuracy will be essential to understand the pathophysiology of ischemia and for directing better methods of managing ischemic heart disease.

Measurement of right ventricular volume in human explanted hearts using ultrafast cine computed tomography.

The quantitative measurement of right ventricular (RV) volume has been attempted by a number of methods, including nuclear magnetic resonance imaging, contrast angiography, echocardiography, and radionuclide angiography. All of these methods have limitations. Ultrafast cine computed tomographic (CT) scan is a new technology that may have an important role in on-line ventricular volume measurements. Twelve human explanted hearts, fixed in formalin, were subjected to ultrafast cine CT scans to estimate RV volume. The volumes derived from the CT scans were compared with actual fluid volumes needed to fill the RV volume measurements. All measurements were conducted independently by two observers. Actual RV volumes in the 12 hearts ranged from 29.8 ml to 174.6 ml. A strongly significant correlation between actual volume and CT volume was seen (r = 0.99). Agreement between observers was also seen to be highly significant (r = 0.992). Limitations to accurate in vivo assessment due to bolus injection of contrast medium might include alterations in ventricular pressure change. Similarly, differentiation of the endocardial border with contrast may not be as sharp as that with an air-tissue interface. This study demonstrates that RV volumes can be reliably determined by ultrafast cine CT scans in explanted hearts. On-line systolic and diastolic volumes and thus stroke volume, ejection fraction, etc, can be accurately defined independent of cardiac orientation. This technique offers opportunities to study ventricular function under various conditions.

Transfer-function analysis of UFCT myocardial time-density curves by time-varying recursive least squares analysis.

Techniques which assume linear, time-invariant systems have been used to characterize indicator dilution pairs. As a basis for fully describing the relation between left ventricular (LV) and myocardial (MYC) time-density curves, produced by an intravenous contrast medium as measured by ultrafast CT, the assumption of time invariance was tested using recursive least squares regression and CUSUM, a test for time variability of regression parameters. Using data from anesthetized dogs with concomitant microsphere information, constant and time-varying regression models, MYC(t) = b(t)LV(t-1), were generated from time-density curves of flows from two groups: Group 1 (MBF < 2 ml/min/gm, n = 11) and Group 2 (MBF > 2 ml/min/gm, n = 10). The time-varying regression models had reduced root mean square error: 0.6 +/- 1.1 and 0.5 +/- 0.8 versus 7.3 +/- 3.5 and 4.1 +/- 1.6 for Groups 1 and 2, respectively. Significant time variability (p < 0.05) by CUSUM was found in 9/11 Group 1 models and 7/10 Group 2 models. Myocardial blood volume was estimated as the average value of b(t) over the rising portion of the LV curve. Myocardial blood flow was then calculated as myocardial blood volume divided by coronary transit time, determined from gamma variate fits of the LV and scaled, shifted LV curve, with excellent results over a wide range of flows (r = 0.93, y = 0.92 x + 0.28, range of 0.4 to 6.7 ml/min/gm). These results show that measurements of increased myocardial blood flow are possible with an intravenous contrast media, and that movement of contrast medium from intravascular space to extravascular space occurs during the course of the contrast medium's first pass.

Accuracy and reproducibility of precordial percussion and palpation for detecting increased left ventricular end-diastolic volume and mass. A comparison of physical findings and ultrafast computed tomography of the heart.

OBJECTIVE: To assess the accuracy and reproducibility of indirect definitive precordial percussion in detecting increased left ventricular end-diastolic volume (LVEDV), left ventricular mass (LVM), and left ventricular end-diastolic wall thickness (LVEDWT), and to compare it with palpation of the apical impulse. DESIGN: Descriptive study. SETTING: Hospitals and clinics of a university medical center. PATIENTS: Convenience sample of 103 patients (62 men and 41 women) referred for ultrafast computed tomography (CT) of the heart. INTERVENTIONS: Percussion dullness distance from the midsternal line in the left fourth through sixth intercostal spaces, distance of the apical impulse from the midsternal line, and apical impulse diameter in the left lateral decubitus position were measured on all patients. Measurements of LVEDV, LVM, and LVEDWT were taken using ultrafast CT of the heart. Investigators performing the physical diagnostic maneuvers were blinded to the clinical history and CT results, and investigators performing the CT scans were blinded to physical findings. RESULTS: Percussion dullness distance in the left fifth intercostal space was the best discriminator of LVEDV (receiver operating characteristic [ROC] area, 0.680; 95% confidence interval [CI], 0.547 to 0.813), and dullness distance in the left sixth intercostal space was the best discriminator of LVM and LVEDWT (ROC areas, 0.831, 95% CI, 0.674 to 0.988; and 0.849, 95% CI, 0.651 to 0.999, respectively). A percussion dullness distance of greater than 10.5 cm in the left fifth intercostal space detected increased LVEDV or LVM with a sensitivity of 91.3% (95% CI, 70.5% to 98.5%) and a specificity of 30.3% (95% CI, 19.9% to 43.0%). There was moderate concordance between investigators for percussion dullness distance (kappa, 0.57; 95% CI, 0.18 to 0.96). In patients in whom an impulse was palpated, an apical impulse diameter of greater than 3.0 cm in the left lateral decubitus detected increased LVEDV or LVM with a sensitivity of 100% (95% CI, 77.1% to 100%) and a specificity of 40% (95% CI, 23.2% to 59.3%). However, an impulse was palpable in only 53% of cases and showed only slight interobserver reproducibility (kappa, 0.18; 95% CI, 0.0 to 0.58). CONCLUSION: Indirect definitive percussion of the precordium is a sensitive and moderately reproducible maneuver for excluding cardiomegaly due to increased LVEDV or LVM. Although measurement of apical impulse diameter was also sensitive in excluding cardiomegaly, lack of a palpable impulse in many patients and low precision between physicians may limit its utility in clinical practice.

Analysis of regional pulmonary enhancement in dogs by ultrafast computed tomography.

Measurement of regional pulmonary enhancement was made in five anesthetized dogs with intravenous contrast material-enhanced ultrafast computed tomography (CT). Three or four electrocardiogram-gated flow scans were performed in each dog in the prone and supine positions. Immediately after each flow scan was acquired at four levels (8-mm thick slices), 20 times per level, 0.5 mL/kg (10 mL/second) ionic contrast medium was injected into the inferior vena cavae. Each level of each lung was divided into anterior, middle, and posterior regions for time density curve analysis and regional flow estimation. Images were transferred to an off-line workstation for lung pixel colorization and subjective interpretation. There was a statistically significant gravity-related enhancement gradient in both the supine and prone positions; however, the gradient was much greater in the supine position. This study shows that gravity-related contrast medium enhancement gradients in the lung can be demonstrated by ultrafast CT.

Myocardial color perfusion images from ultrafast computed tomography.

This article presents a new method for visualization of myocardial perfusion information from ultrafast computed tomography (UFCT). Changes in myocardial density produced by intravenous contrast medium enhancement were color coded selectively and displayed in a cold to hot spectrum. Color coded images from anesthetized canines with temporarily occluded left anterior descending coronary arteries clearly showed ischemic myocardium. Other regional flow differences such as arrival times and regional heterogeneity of enhancement also were observed. An objective comparison of UFCT and microsphere data was made by the amount of ischemia and by the flow histograms of each method for control and occlusion states. The amount of ischemia detected by UFCT (5.6 +/- 2.3%) was less than that detected by microspheres (7.9 +/- 5.0%). Analysis of variance showed significant differences (P less than 0.05) caused by occluder status but not measurement method. The microsphere occlusion flow histogram was significantly different than the microsphere control and UFCT occlusion histograms at low flows. This preliminary evaluation shows promise for optimising visualization of flow patterns within the myocardium.

Reproducibility of left ventricular myocardial volume and mass measurements by ultrafast computed tomography.

Ultrafast computed tomography has been reported to be an accurate method of measuring left ventricular mass in dogs. To assess the interstudy, intraobserver and interobserver variability of left ventricular myocardial mass measurements in humans, left ventricular myocardial volume was measured three times within 24 h in 16 patients with ischemic heart disease. The mean percent difference of the mean of the three studies performed was -0.01 +/- 1.4% (range -2.9% to 3.6%). The regression analysis for the intraobserver variability at baseline was: Y = -4.33 + 1.03X; r = 0.99, SEE = 3.5 ml. The mean percent difference of the mean of the two sets of measurements performed by two independent observers was 0.28 +/- 2.1% (range -4.35% to 4.35%). The interobserver variability excluding papillary muscles at baseline study was: Y = -4.34 + 1.06X; r = 0.99, SEE = 1.5 ml. The regression analysis with versus without papillary muscles showed: Y = -8.72 + 0.97X; r = 0.96, SEE = 2.6 ml. Regression analysis to assess the variability of 24-h studies at end-systole versus end-diastole revealed: Y = 3.07 + 0.94X; r = 0.97, SEE = 1.8 ml. In conclusion, ultrafast computed tomography is a minimally invasive technique, with very low interstudy, intraobserver and interobserver variability for left ventricular myocardial volume and mass determinations in serial studies.

Validation of ultrafast computed tomographic left ventricular volume measurement.

Left ventricular volume has been measured with ultrafast computed tomography. However, the accuracy with which this can be done is unknown. We therefore imaged with ultrafast computed tomography 11 rectangular phantoms, 20 to 225 ml, and 17 left ventricular casts, 15 to 112 ml. Two observers planimetered serial tomographic images and computed volume from sequential tomograms. There was no significant inter- or intraobserver difference in measurement of phantoms. Deviation of ultrafast computed tomographic volume from true phantom volume was -0.1 +/- 3.5% SD, range 9.0 to -7.6%. Correlation of true phantom volume with ultrafast computed tomographic volume was 0.99, SEE = 1.9 ml. No significant difference was observed between merged and single ultrafast computed tomographic scanning sequences. Left ventricular cast volume determined by ultrafast computed tomography deviated from true volume by 6% +/- 20%, range 54% to -45%. Correlation of true volume with ultrafast computed tomographic volume was 0.99, SEE = 5.1 ml. There was no interobserver significant difference in measurement of left ventricular cast volume. Correlation between ultrafast computed tomographic volume and cineradiographic volume of the same left ventricular casts was 0.99, SEE = 4.4 ml. Thus, phantom volumes can be measured accurately without significant intra- or interobserver variation. Merged scanning sequences did not influence volume determination. Left ventricular cast volume determination was comparable to that obtained with cineradiography.

Measurement of myocardial blood flow by UFCT: towards clinical applicability.

This review is designed to be a summary of the research conducted towards establishing ultrafast CT as a clinically appropriate tool for measuring myocardial blood flow. The methods and techniques used in the animal validation studies are presented. The results will be critically analyzed and the conclusions discussed. The proposed improvements to flow calculation algorithms will also be addressed. Technical improvements and experimental research needed will also be addressed.

Acute hemodynamic effects of pindolol and propranolol in patients with dilated cardiomyopathy: relevance of intrinsic sympathomimetic activity.

The administration of beta-blocking agents to patients with poor left ventricular (LV) function may result in clinical and hemodynamic deterioration. The beta antagonist pindolol has intrinsic sympathomimetic activity (ISA) and therefore may be better tolerated. To test this hypothesis 30 patients with a precatheterization diagnosis of dilated cardiomyopathy were randomly assigned to three groups to receive intravenous injections of placebo, propranolol, or pindolol. The baseline ejection fraction and hemodynamics were similar for all groups. For propranolol 1 mg, 2 mg, 3 mg, and 4 mg doses were given 5 minutes apart until a maximum dose of 10 mg was reached, until a 25% reduction in the heart rate or mean arterial pressure occurred, or until clinical deterioration developed. For pindolol, 0.1 mg, 0.2 mg, 0.3 mg, and 0.4 mg boluses were used with the same end points. Baseline hemodynamics were measured and repeated 15 minutes after the last dose of each drug was administered. The mean number of doses given was similar for both groups: 3.3 doses for the propranolol group and 3.4 for the pindolol group. Compared to propranolol, pindolol caused less of a reduction in heart rate, cardiac output, cardiac index, stroke volume index, and stroke work index and less of an increase in the mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, and pulmonary vascular resistance; there was a decrease in systemic vascular resistance. These differences were statistically significant for changes in heart rate, right atrial pressure, cardiac index, and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of myocardial blood flow by ultrafast computed tomography.

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.

Determination of cardiac output by ultrafast computed tomography.

Three methods of determining cardiac output were compared in six anesthetized dogs (23-28 kg) for the purpose of evaluating the ability of ultrafast computed tomography to measure cardiac output at three points of the circulation: pulmonary artery, left ventricle, and descending aorta. Computed tomography cardiac output is calculated by indicator dilution analysis of an iodinated contrast bolus time-density curve. Computed tomography cardiac output was compared to thermodilution and radioactive microsphere cardiac output methods. The results show very good agreement between thermodilution and computed tomography methods (r = .90) and good agreement between microsphere and computed tomography (r = .88). Comparison of computed tomography cardiac output measurements from the left ventricle and pulmonary artery was excellent (r = .99), as were measurements from the left ventricle and descending aorta (r = .97). This study also showed minimal interlevel scan-density response variability (3%) and minimal variability between experiments (7%). Therefore, it is concluded that cardiac output can be accurately measured at many points in the blood pool by ultrafast computed tomography.